Abstract
It has been suggested that oxidative stress products play an important role in the etiology of epilepsy. We investigated the effects of selenium (Se) administration on topiramate (TPM)- and pentylentetrazol (PTZ)-induced brain toxicity in rats. Forty male Wistar rats were divided into five equal groups. The first and second groups were used as the control and PTZ groups, respectively. TPM, 50 mg, and Se, 0.3 mg, were administered to rats constituting the third and fourth groups, respectively, for 7 days. The combination of 50 mg TPM and Se was given to animals in the fifth group for 7 days. At the end of 7 days all groups except the first received a single dose of PTZ. Brain cortex samples were taken at 3 h of PTZ administration. PTZ resulted in a significant increase in brain cortex and microsomal lipid peroxidation (LP) levels, number of spikes, and epileptiform discharges on the EEG, although brain cortex vitamin E, brain cortex and microsomal reduced glutathione (GSH), and microsomal calcium (Ca) levels, Ca2+-ATPase activities, and latency to first spike on the EEG were decreased by PTZ. LP, GSH, vitamin E, and Ca levels and Ca2+-ATPase activities were increased by both Se and TPM, although vitamin A and C concentrations were increased by Se only. There were no effects of TPM and Se on brain cortex and microsomal glutathione peroxidase, brain cortex nitric oxide, or β-carotene levels. In conclusion, TPM and selenium caused protective effects on PTZ-induced brain injury by inhibiting free radical production, regulating calcium-dependent processes, and supporting the antioxidant redox system.
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Abbreviations
- GSH:
-
Glutathione
- GSH-Px:
-
Glutathione peroxidase
- LP:
-
Lipid peroxidation
- MDA:
-
Malondialdehyde
- NO:
-
Nitric oxide
- PMCA:
-
Plasma membrane Ca2+-ATPase
- PTZ:
-
Pentylentetrazol
- ROS:
-
Reactive oxygen species
- SOD:
-
Superoxide dismutase
- TPM:
-
Topiramate
- VGCC:
-
Voltage gated calcium channels
References
Akbas SH, Yegin A, Ozben T (2005) Effect of pentylenetetrazol-induced epileptic seizure on the antioxidant enzyme activities, glutathione and lipid peroxidation levels in rat erythrocytes and liver tissues. Clin Biochem 38:1009–1014
Armağan A, Kutluhan S, Yılmaz M, Yılmaz N, Bülbül M, Vural H, Soyupek S, Nazıroğlu M (2008) Topiramate and vitamin E modulates antioxidant enzymes, nitric oxide and lipid peroxidation in pentylentetrazol-induced nephrotoxicity in rats. Basic Clin Pharm Toxicol 103:166–170
Arrigoni O, De Tullio MC (2002) Ascorbic acid: much more than just an antioxidant. Biochim Biophys Acta 1569:1–9
Ashrafi MR, Shams S, Nouri M, Mohseni M, Shabanian R, Yekaninejad MS, Chegini N, Khodadad A, Safaralizadeh R (2007) A probable causative factor for an old problem: selenium and glutathione peroxidase appear to play important roles in epilepsy pathogenesis. Epilepsia 48:1750–1755
Brown MR, Cohen HJ, Lyons JM, Curtis TW, Thunberg B, Cochran WJ, Klish WJ (1986) Proximal muscle weakness and selenium deficiency associated with long term parenteral nutrition. Am J Clin Nutr 43:549–554
Cardile V, Pavone A, Renis M, Maci T, Perciavalle V (2001) Effects of gabapentin and topiramate in primary rat astrocyte cultures. Neuroreport 12:1705–1708
Colegrove SL, Albrecht MA, Friel DD (2000) Dissection of mitochondrial Ca2+ uptake and release fluxes in situ after depolarization-evoked [Ca2+]i elevations in sympathetic neurons. J Gen Physiol 115:351–370
Czernichow S, Hersberg S (2001) Interventional studies concerning the role of antioxidant vitamins in cardiovascular disease: a review. J Nutr Health Aging 5:188–195
Deniz Onay B, Tasdemir E, Tümer C, Bilgin HM, Atmaca M (2008) Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides 29:448–455
Desai ID (1984) Vitamin E analysis methods for animal tissues. Methods Enzymol 105:138–147
Doğru Pekiner B, Daş Evcimen N, Nebioğlu S (2005) Diabetes-induced decrease in rat brain microsomal Ca2+-ATPase activity. Cell Biochem Funct 23:239–243
Duchen MR (2000) Mitochondria and calcium: from cell signalling to cell death. J Physiol 529:57–68
Dykens JA (1994) Isolated cerebral and cerebellar mitochondria produce free radicals when exposed to elevated Ca2+ and Na+: implications for neurodegeneration. J Neurochem 63:584–591
Eraković V, Zupan G, Varljen J, Simonić A (2003) Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids, superoxide dismutase, and glutathione peroxidase activity. Neurochem Int 42:173–178
Eren I, Naziroglu M, Demirdaş A (2007) Protective effects of lamotrigine, aripirazole and escitalopram on depression- induced oxidative stress in rat brain. Neurochem Res 32:1188–1195
Frantseva MV, Perez Velazquez JL, Tsoraklidis G, Mendonca AJ, Adamchik Y, Mills LR, Carlen PL, Burnham MW (2000) Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97:431–435
Ilhan A, Gurel A, Armutcu F, Kamisli S, Iraz M (2005) Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice. Neuropharmacology 49:456–464
Isokawa M (2005) N-Methyl-D-aspartic acid-induced and Ca-dependent neuronal swelling and its retardation by brain-derived neurotrophic factor in the epileptic hippocampus. Neuroscience 131:801–812
Jagota SK, Dani HM (1982) A new colorimetric technique for the estimation of vitamin C using Folin phenol reagent. Anal Biochem 127:178–182
Kharatishvili I, Immonen R, Gröhn O, Pitkänen A (2007) Quantitative diffusion MRI of hippocampus as a surrogate marker for post-traumatic epileptogenesis. Brain 130(Pt 12):3155–3168
Kirkby RD, Carroll DM, Grossman AB, Subramaniam S (1996) Factors determining proconvulsant and anticonvulsant effects of inhibitors of nitric oxide synthase in rodents. Epilepsy Res 24:91–100
Kovács R, Schuchmann S, Gabriel S, Kann O, Kardos J, Heinemann U (2002) Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. J Neurophysiol 88:2909–2918
Kubera M, Budziszewska B, Jaworska-Feil L, Basta-Kaim A, Leśkiewicz M, Tetich M, Maes M, Kenis G, Marciniak A, Czuczwar SJ, Jagła G, Nowak W, Lasoń W (2004) Effect of topiramate on the kainate-induced status epilepticus, lipid peroxidation and immunoreactivity of rats. Pol J Pharmacol 56:553–561
Kürekçi AE, Alpay F, Tanindi S, Gökçay E, Ozcan O, Akin R, Işimer A, Sayal A (1995) Plasma trace element, plasma glutathione peroxidase, and superoxide dismutase levels in epileptic children receiving antiepileptic drug therapy. Epilepsia 366:600–604
Lawrence RA, Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71:952–958
Lee SR, Kim SP, Kim JE (2000) Protective effect of topiramate against hippocampal neuronal damage after global ischemia in the gerbils. Neurosci Lett 281:183–186
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin-phenol reagent. J Biol Chem 193:265–275
Maertens P, Dyken P, Graf W, Pippenger C, Chronister R, Shah A (1995) Free radical, anticonvulsants, and the neuronal ceroid-lipofuscinoses. Am J Med Genet 57:225–228
Nazıroğlu M (2003) Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats: protective role of vitamins C and E and selenium. Biol Trace Elem Res 94:61–72
Nazıroğlu M (2007a) Molecular mechanisms of vitamin E on intracellular signaling pathways in brain. In: Goth L (ed) Reactive oxygen species and diseases. Research Signpost Press, Kerala, India, pp 239–256
Nazıroğlu M (2007b) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001
Nazıroğlu M, Uğuz AC, Gokçimen A, Bülbül M, Karatopuk DU, Türker Y, Cerçi C (2008) Tenoxicam modulates antioxidant redox system and lipid peroxidation in rat brain. Neurochem Res 33:1832–1837
Niggli V, Adunyah ES, Penniston JT, Carafoli E (1981) Purified (Ca2+-Mg2+)-ATPase of the erythrocyte membrane. Reconstitution and effect of calmodulin and phospholipids. J Biol Chem 256:395–401
Ono H, Sakamato A, Sakura N (2000) Plasma total glutathione concentrations in epileptic patients taking anticonvulsants. Clin Chim Acta 298:135–143
Özmen I, Nazıroğlu M, Alicı HA, Sahin F, Cengiz M, Eren İ (2007) Spinal morphine administration reduces the fatty acid contents in spinal cord and brain in rabbits due to oxidative stress. Neurochem Res 32:19–25
Öztaş B, Kiliç S, Dural E, Ispir T (2001) Influence of antioxidants on the blood-brain barrier permeability during epileptic seizures. J Neurosci Res 66:674–678
Patel M (2004) Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures. Free Radic Biol Med 37:1951–1962
Pavone A, Cardile V (2003) An in vitro study of new antiepileptic drugs and astrocytes. Epilepsia 44(Suppl 10):34–39
Placer ZA, Cushman L, Johnson BC (1966) Estimation of products of lipid peroxidation (malonyl dialdehyde) in biological fluids. Anal Biochem 16:359–364
Schweizer U, Bräuer AU, Köhrle J, Nitsch R, Savaskan NE (2004a) Selenium and brain function: a poorly recognized liaison. Brain Res Brain Res Rev 45:164–178
Schweizer U, Michaelis M, Köhrle J, Schomburg L (2004b) Efficient selenium transfer from mother to offspring in selenoprotein-P-deficient mice enables dose-dependent rescue of phenotypes associated with selenium deficiency. Biochem J 378(Pt 1):21–26
Sedlak J, Lindsay RHC (1968) Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmann’s reagent. Anal Biochem 25:192–205
Suzuki J, Katoh N (1990) A simple and cheap method for measuring vitamin A in cattle using only a spectrophotometer. Jpn J Vet Sci 52:1282–1284
Uma Devi P, Pillai KK, Vohora D (2006) Modulation of pentylenetetrazole-induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N-acetylcysteine. Fund Clin Pharmacol 20:247–253
Verrotti A, Basciani F, Trotta D, Pomilio MP, Morgese G, Chiarelli F (2002) Serum copper, zinc, selenium, glutathione peroxidase and superoxide dismutase levels in epileptic children before and after 1 year of sodium valproate and carbamazepine therapy. Epilepsy Res 48:71–75
Weiergräber M, Henry M, Krieger A, Kamp M, Radhakrishnan K, Hescheler J, Schneider T (2006) Altered seizure susceptibility in mice lacking the Ca(v)2.3 E-type Ca2+ channel. Epilepsia 47:839–850
Whanger PD (2001) Selenium and the brain: a review. Nutr Neurosci 4:81–97
White HS, Smith MD, Wilcox KS (2007) Mechanisms of action of antiepileptic drugs. Int Rev Neurobiol 81:85–110
Willmore LJ, Rubin JJ (1981) Antiperoxidant pretreatment and iron-induced epileptiform discharges in the rat: EEG and histopathologic studies. Neurology 31:63–69
Yatin SM, Varadarajan S, Butterfield DA (2000) Vitamin E prevents Alzheimer’s amyloid beta-peptide (1–42)-induced neuronal protein oxidation and reactive oxygen species production. J Alzheimers Dis 2:123–131
Acknowledgments
This study was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK; SBAG-HD-228). The suthors wish to thank Ph.D. students Ömer Çelik and A Cihangir Uğuz, Department of Biophysics, Suleyman Demirel University, for help with analyses.
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Nazıroğlu, M., Kutluhan, S. & Yılmaz, M. Selenium and Topiramate Modulates Brain Microsomal Oxidative Stress Values, Ca2+-ATPase Activity, and EEG Records in Pentylentetrazol-Induced Seizures in Rats. J Membrane Biol 225, 39–49 (2008). https://doi.org/10.1007/s00232-008-9132-6
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DOI: https://doi.org/10.1007/s00232-008-9132-6